| Project/Area Number |
04404026
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
HAYAISHI Osamu Osaka Bioscience Institute Director, 所長 (40025507)
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| Co-Investigator(Kenkyū-buntansha) |
OSAKA Toshimasa Osaka Bioscience Institute Department of Molecular Behavioral Biology Researcher, 第2研究九部, 研究員 (30152101)
WATANABE Kikuko Osaka Bioscience Institute Department of Molecular Behavioral Biology Researcher, 第2研究部, 研究員 (90211672)
MATSUMURA Hitoshi Osaka Bioscience Institute Department of Molecular Behavioral Biology Vice-Head, 第2研究部, 研究副部長 (50173886)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥28,000,000 (Direct Cost: ¥28,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1992: ¥20,000,000 (Direct Cost: ¥20,000,000)
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| Keywords | Prostaglandin D_2 / Prstaglandin E_2 / Sleep / Wakefulness / Prostaglandin D synthase / Subarachnoid space / beta-Trace / Cerebrospinal fluid / プロスタグランジン / ニューロン / 軟膜 / マイクロダイアリシス / 脈絡叢 / 神経回路網 / 視束前野 / セロトニン |
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| Research Abstract |
We previously hypothesized that prostaglandin (PG) D_2 and PGE_2 are endogenous sleep-wake regulating substances. In this study, we examined the site of action of the sleep-promoting effect of PGD_2 with more than 200 rats and found that continuous and bilateral infusion of PGD_2 into the subarachnoid space under the rostal basal forebrain increased slow-wave sleep up to the maximum level that can be attained physiologically. This PGD_2-sensitive, sleep-promoting zone spreads beneath the horizontal limb of the diagonal band and even towards rostral under the basal forebrain. Thus, the site of action was confined in the ventral region of the rostral basal forebrain. Our group also demonstrated that the brain type PGD synthase, which is the major enzyme responsible for the synthesis of PGD_2 in the brain, is crucial for the maintenance of physiological sleep : i.e., administration of inhibitors of this enzyme caused total insomnia. By use of in situ hybridization and immunohistochemical staining, it was shown that this enzyme is mainly located in the choroid plexus, leptomeninges, and, in less degree, the white matter. It was also demonstrated that the cerebrospinal fluid (CSF) exhibited PGD synthase activity with a highest specific activity among various brain tissues examined. The second most abundant protein in the CSF,which was known as beta-trace, was shown to be identical to the PGD synthase itself. Based on the results of this reserach, it is hypothesized that PGD_2 synthesized in the surface layr of the brain acts as a sleep promoter at the ventral surface zone of the rostral basal forebrain, and that the PGD_2 and PGD synthase (or beta-trace) in the CSF also play important roles in the sleep-wake regulation.
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